In 2011, the reporting to the Languedoc-Roussillon Regional Health Agency (ARS) of two symptomatic cases of acute hepatitis E among operating room staff at a hospital warranted an epidemiological investigation, screening of staff, and an assessment of the risk of healthcare-associated infection in such a setting. Among the 59 staff members, case finding identified 5 additional staff members with serological test results consistent with recent hepatitis E virus infection, and 5 with an infection considered to be past, in a context of high regional prevalence linked to specific dietary habits. The epidemiological investigation did not reveal an association between the occurrence of recent hepatitis E and shared meals, and could not attribute these cases to a common food source. Invasive procedures were suspended for healthcare workers exhibiting clinical symptoms suggestive of viral hepatitis or a positive viral load until their test results turned negative, while a reminder of standard precautions combined with enhanced disinfection protocols was implemented to prevent any risk of cross-transmission. (R.A.)